The electrical behavior of cells and cell membranes is of profound importance in basic research as well as in modern drug development. A specific area of interest in this field is in the study of ion channels and transporters. Ion channels are protein-based pores found in the cell membrane that are responsible for maintaining the electrochemical gradients between the extracellular environment and the cell cytoplasm. Ion channels are passive elements in that, once opened, ions flow in the direction of existing electrochemical gradients.
The study of ion channels is a very diverse and prolific area encompassing basic academic research as well as biotechnical and pharmaceutical research. Electrophysiology is performed on isolated cell membranes or vesicles as well as on synthetic membranes where solubilized channels are reconstituted into a manufactured membrane. Instrumentation for automated, high-throughput studies of ion channels have been developed and may be referred to as high-throughput electrophysiological measurement systems.
Automated high-throughput electrophysiology measurement systems may employ patch plates clamped to a plenum. The space between the patch plate and the plenum may be filled with an electrically conductive buffer solution to form an electrical connection between electrodes in the plenum and target cells contained in the patch plate. The electrodes may thus measure electrical properties of target cells during assays.
At the conclusion of the assay, a robotic plate handler may transfer the patch plate to other locations at the system. Residual buffer solution on the bottom of the patch plate, however, may drip onto sensitive components of the system as the robotic plate handler transfers the patch plate between locations, which can damage those components or create contamination issues. Additionally, buffer solution that remains in the plenum may entrap bubbles when the plenum is subsequently refilled. Bubbles entrapped in the plenum may cause a lack of electrical continuity between electrodes, which can result in failures during electrophysiology testing. Moreover, electrodes of the system may degrade over time due to chemical and electrical activity at the electrodes. As a result, the electrodes may need to be periodically reconditioned between assays. Therefore, there is a need for conditioning the patch plate, plenum, and other components of an automated high-throughput electrophysiology measurement system.
Automated high-throughput electrophysiology measurement systems may include robotic plate handlers to manipulate microtitre plates (“microplates”) and other transportable components (e.g., pipette tip boxes) during assays. Successful automation of assays depends on the ability of the robotic plate handler to accurately load and place the microplates (or other components) into various devices or locations of the system, which may involve accurately positioning and orienting the microplates often to within precise tolerances.
As the robotic plate handler moves the microplates between devices, slight positioning offsets and orientation offsets may occur and accumulate. Position offsets and orientation offsets can result in position and orientation errors when attempting to load and place the microplates. To avoid position errors and orientation errors, devices to reposition and reorient the microplates may be employed. Conventional devices may include passive features to reposition and reorient the microplates. These conventional devices, however, may not be equipped to overcome the dimensional tolerances of standard microplates, which can vary in length and width by up to, for example, 1 millimeter (mm) or more.
Furthermore, microplates may need to be repositioned or reoriented in some situations in order to align the microplates with devices oriented at incompatible angles. Moreover, microplates may include a bar code applied to one side, and because there is no standardized position for the bar code, microplates may need to be reoriented in order to bring the bar code within view of a bar code reader. Therefore, a need also exists for apparatuses and methods to automatically reposition and reorient microplates and other similarly-sized components.